We have found that a large variety of agents can stimulate DNA synthesis in cultures of chick embryo fibroblasts. These agents also stimulate a wide array of metabolic pathways in the cells including their differentiated functions. We have been conducting a search for an underlying reaction which is capable of regulating many independent cellular activities, and this past year we have produced evidence that this reaction is the activation of magnesium (Mg) in the cell. This year we shall be measuring the concentrations of Mg, Ca, Na and K in cells under various conditions. We shall also be using enzyme equilibrium measurements to estimate the free Mg in cells. We shall also be determining whether Mg deprivation affects precisely the same biochemical steps as does removal of serum, low pH or high population density. BIBLIOGRAPHIC REFERENCES: Kamine, James and H. Rubin. Magnesium required for serum-stimulation of growth in cultures of chick embryo fibroblasts. Nature 263, 143-145, 1976. Rubin, H. and T. Koide. Mutual potentiation by magnesium and calcium of growth in animal cells. Proc. Nat. Acad. Sci. U.S. 73, 168-172, 1976.